Nitric oxide (NO∙), initially known as endothelium derived relaxing factor (EDRF), is biosynthesized within the body from L-arginine and oxygen by a variety of nitric oxide synthase enzymes (Col lier and Vallance, 1991). Nitric oxide is a gaseous chemical compound that acts as an important signaling molecule within the human body. Nitric oxide has been shown to decrease platelet and leukocyte adhesion, as well as to decrease the proliferation of smooth muscle cells. These effects are important in reference to decreasing clot and lesion formation within blood vessels, which may be associated with non-fatal and fatal outcomes (e.g., heart attack, stroke). Recent evidence also indicates that NO∙ may be involved in both glucose and fatty acid oxidation (Jobgen et al., 2006). Although, perhaps the most well studied effect of NO∙ is in facilitating vasodilation (opening of blood vessels).
The endothelium (inner layer) of blood vessels is involved in NO∙ production, which acts on vascular smooth muscle cells to promote vasodilation. For this reason alone, nitric oxide has received considerable attention over the past 20+ years from scientists. In fact, NO was recognized as “molecule of the year” by Science in 1992. Additionally, the Nobel Prize in Physiology or Medicine was awarded in 1998 to Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries related to NO∙. Over the past 5 years in particular, NO has received a great deal of attention from health and fitness enthusiasts, as well as from sports supplement companies who widely market products cl aiming to increase NO production. In this regard, the primary desired effect is the potential increase in blood flow.
It is evident that the majority of such products contain various forms of L-arginine as the chief ingredient. Unfortunately, as discussed below, this may not be appropriate when considering all variables know to affect the response to L-arginine treatment (e.g., dosage, route of administration, species studied). Equally important, although L-arginine is the precursor to NO∙ biosynthesis, it has been suggested that this amino acid is not the rate limiting component (Kurz and Harrison, 1997) and that nitric oxide synthase enzymes may be most important to NO∙ biosynthesis. Therefore, adding excess L-arginine may do little to promote increased NO∙ production, as most individuals already have adequate L-arginine available for NO∙ biosynthesis. What they may need is an increase in certain enzymes that appear to ultimately control NO∙ production. The supposed “effect” that individuals may experience when using many of the marketed products may be more dependent on the sugar contained within the product, as opposed to the L-arginine. This is because sugar intake results in an insulin spike, and insulin itself has been shown to yield a vasodilating effect (Giugliano et al., 1997; Steinberg et al., 1994).
Despite this, it is evident that dietary supplements marketed to increase NO∙ production are rampant within the supplement industry. In fact, a quick scan of many of the popular bodybuilding magazines indicates that in any given month there can be more than 30 pages of advertisements that focus solely on this particular class of supplements! As with many dietary supplements, the scientific evidence for effect for these products is virtually nonexistent. Of course, some of the chief ingredients found within some of these products may have been shown to result in a measurable increase in NO∙ or an increase in blood flow. But a careful review of the original investigations indicates that the dosing suggested by the manufacturer of the product is often FAR less than that used in the original investigation. More importantly, the route of administration is often different. That is, many original investigations using a given ingredient have used intravenous injection and not oral intake, as is being marketed by supplement companies. This is of particular importance, as L-arginine at an oral dosage of only 10 grams per day has been noted to have an unpleasant taste and in some cases result in gastric distress (Robinson et al., 2003). It has also been reported that oral intake of L-arginine of 20+ grams per day results in arginine absorption that is highly variable across subjects, and does not result in any significant increase in vasodilation (Adams et al., 1995; Chin-Dusting e t al., 1996), unlike findings from many studies involving intravenous injection. Other work involving direct comparisons between intravenous and oral intake of L-arginine agrees with these findings (Bode-Boger et al., 1998), indicating no effect of oral L-arginine intake on vasodilation, partly due the fact that oral L-arginine bioavailability is only ~68%. Hence, based on the available evidence, it seems unlikely that oral L-arginine intake will result in any improvement in blood flow. Lastly, some of the original investigations have used animals (typically rodents) as test subjects and not humans, or have involved experiments in vitro (i.e., outside of a living organism). Generalizations to humans cannot always be made from such studies. Collectively, the fact remains that no nutritional supplements marketed to increase NO∙ have been shown in a controlled laboratory study involving human subjects to increase blood levels of NO
